RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at dif...

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Main Authors: Marisa M Brockmann, Marta Maglione, Claudia G Willmes, Alexander Stumpf, Boris A Bouazza, Laura M Velasquez, M Katharina Grauel, Prateep Beed, Martin Lehmann, Niclas Gimber, Jan Schmoranzer, Stephan J Sigrist, Christian Rosenmund, Dietmar Schmitz
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-09-01
Series:eLife
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Online Access:https://elifesciences.org/articles/43243
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author Marisa M Brockmann
Marta Maglione
Claudia G Willmes
Alexander Stumpf
Boris A Bouazza
Laura M Velasquez
M Katharina Grauel
Prateep Beed
Martin Lehmann
Niclas Gimber
Jan Schmoranzer
Stephan J Sigrist
Christian Rosenmund
Dietmar Schmitz
author_facet Marisa M Brockmann
Marta Maglione
Claudia G Willmes
Alexander Stumpf
Boris A Bouazza
Laura M Velasquez
M Katharina Grauel
Prateep Beed
Martin Lehmann
Niclas Gimber
Jan Schmoranzer
Stephan J Sigrist
Christian Rosenmund
Dietmar Schmitz
author_sort Marisa M Brockmann
collection DOAJ
description All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at different central murine synapses and thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active zone. We suggest that differences in the active zone organization may dictate the role a protein plays in synaptic transmission and that differences in active zone architecture is a major determinant factor in the functional diversity of synapses.
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spelling doaj.art-ebd13371dad64488b7c36a53f858e4062022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.43243RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapsesMarisa M Brockmann0https://orcid.org/0000-0002-1386-5359Marta Maglione1Claudia G Willmes2Alexander Stumpf3Boris A Bouazza4Laura M Velasquez5M Katharina Grauel6https://orcid.org/0000-0003-3542-0606Prateep Beed7Martin Lehmann8Niclas Gimber9Jan Schmoranzer10Stephan J Sigrist11https://orcid.org/0000-0002-1698-5815Christian Rosenmund12https://orcid.org/0000-0002-3905-2444Dietmar Schmitz13Institut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyFreie Universität Berlin, Institut für Biologie, Berlin, Germany; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany; NeuroCure Cluster of Excellence, Berlin, GermanyDZNE, German Center for Neurodegenerative Diseases, Berlin, GermanyNeuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyInstitut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyNeuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyInstitut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyNeuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, GermanyNeuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyNeuroCure Cluster of Excellence, Berlin, GermanyFreie Universität Berlin, Institut für Biologie, Berlin, Germany; NeuroCure Cluster of Excellence, Berlin, Germany; DZNE, German Center for Neurodegenerative Diseases, Berlin, GermanyInstitut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; NeuroCure Cluster of Excellence, Berlin, GermanyNeuroCure Cluster of Excellence, Berlin, Germany; DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany; Neuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyAll synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at different central murine synapses and thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active zone. We suggest that differences in the active zone organization may dictate the role a protein plays in synaptic transmission and that differences in active zone architecture is a major determinant factor in the functional diversity of synapses.https://elifesciences.org/articles/43243neurotransmitter releaseactive zonevesicle primingcalcium channelhippocampus
spellingShingle Marisa M Brockmann
Marta Maglione
Claudia G Willmes
Alexander Stumpf
Boris A Bouazza
Laura M Velasquez
M Katharina Grauel
Prateep Beed
Martin Lehmann
Niclas Gimber
Jan Schmoranzer
Stephan J Sigrist
Christian Rosenmund
Dietmar Schmitz
RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
eLife
neurotransmitter release
active zone
vesicle priming
calcium channel
hippocampus
title RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
title_full RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
title_fullStr RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
title_full_unstemmed RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
title_short RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses
title_sort rim bp2 primes synaptic vesicles via recruitment of munc13 1 at hippocampal mossy fiber synapses
topic neurotransmitter release
active zone
vesicle priming
calcium channel
hippocampus
url https://elifesciences.org/articles/43243
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